1xjo

Molecule : Aminopeptidase Classification : Hydrolase

Organism : Streptomyces Griseus Bound ligands : CA, MHO, PO4, ZN

Biological function
S. griseus Aminopeptidase (SGAP) (E.C. 3.4.11.-) cleaves the N-terminal amino acid from a peptide or protein, and is specific for larger hydrophobic acids, especially leucine. No cleavage occurs if the next residue is proline.

Structural features
SGAP belongs to the bacterial dinuclear zinc exopeptidase family and the Zn-dependent exopeptidase superfamily. It has a phosphorylase/hydrolase-like α/β fold, consisting of a 3-layer αβα sandwich.

The active site of the enzyme contains two Zn2+ ions with His85 and Asp160 as ligands for one ion, and Glu132 and His247 as ligands for the second ion. Asp97 is a common ligand to both ions. What appears to be a phosphate anion is bound to both zinc atoms, replacing the water molecule/hydroxide ion normally found in this class of enzyme.

The enzyme's activity is modulated by Calcium cations. This structure revealed a calcium binding site near the N-terminus, involving Ile4, Asp262, Asp266, two water molecules, and Asp3. This site, however, is quite distant from the active site, and it was unclear how this might modulate enzymatic activity. Subsequent mutagenesis studies (Arima et al., 2006a, 2006b) revealed a second calcium binding site adjacent to the active site involving Asp173, Asp174, and Glu196. The latter residue was part of the chain (196-202) that could not be seen in electron density maps in 1xjo.

This view illustrates the path the  chain traces from its amino (N) terminus in blue to its carboxy (C) terminus in red.

Biological context
SGAP belongs to the Peptidase_M28b family, and is one of the many proteinases secreted by S. grisues.

Additional Information
Related structures include by homologous chain: 1f2o, 1f2p.

PDB entry information
Exp. Method: X-ray diffraction

Authors: H.M.Greenblatt, O.Almog, B.Maras, A.Spungin-Bialik, D.Barra, S.Blumberg, G.Shoham

R-value: 0.141 (work)

Date: Jun 23, 1996

Space group: P41212

Crystal cell:

Links

 * 1xjo at OCA